Healthcare-associated infections in Africa: a systematic review and meta-analysis of point prevalence studies

Background There is limited data to describe the point-prevalence of healthcare-associated infections (HAIs) among patients at a regional level in Africa. This study estimated the pooled prevalence of HAIs and described the distribution of HAIs as well as the pathogens identified from African studies. Methods PubMed, Scopus and Google Scholar databases were searched to find point-prevalence studies of HAIs in Africa. Studies conducted in Humans that reported the prevalence of HAIs among hospitalized patients and published in English language from January 2010 to March 2022 were selected. Longitudinal studies of HAIs and unpublished studies were excluded. The reference list of the selected studies was checked to find additional studies. A meta-analysis was conducted using RevMan 5.4 and the pooled prevalence of HAIs was determined using a random effect model. Results Of the 6094 articles identified from the databases, fifteen eligible articles were selected. The studies were conducted in the North, South, East and West African regions with Tunisia (n = 4) and South Africa (n = 2) having the highest number of studies. Most of the studies (n = 12, 80.0%) had good quality. The pooled prevalence of HAIs was 12.76% (95% confidence interval [CI] 10.30–15.23) with a high degree of heterogeneity (I2 = 90.0%). The prevalence of HAIs varied between wards with the highest rate found in the ICU (25.2%–100%), followed by neonatal ICU/ward (7.0%–53.6%) and paediatric medical ward (2.7%–33.0%). Surgical site infection was the most common HAIs and accounted for 41.6% of all HAIs (95% CI 23.55–59.80), followed by bloodstream infection (17.07%, 95% CI 11.80–22.33) and respiratory tract infections/pneumonia (17.04%, 95% CI 13.21–20.87). Recent hospitalization (adjusted odds ratio [AOR]: 4.17, 95% CI 1.85–9.41), presence of peripheral vascular catheter (AOR: 2.87, 95% CI 1.54–5.36) and having diabetes mellitus (AOR: 2.46, 95% CI 1.45–4.17) were the strongest predictors of HAIs in Africa. Only 37.9% of HAIs had documented positive microbiological culture result with gram negative bacteria including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter been the most common microorganisms and accounted for 40%–100% of the pathogens. Conclusions The pooled point-prevalence of HAIs in Africa is more than two times higher than the rate reported in developed countries. The prevalence varied between the countries and was highest in the ICU and neonatal ICU/ward. Surgical site infection and bloodstream infection were the most common HAIs reported in African studies. Recent hospitalization, presence of peripheral vascular catheter and having diabetes mellitus were the strongest predictors of HAIs in African studies. Most of the HAIs are preventable with appropriate infection control measures and antimicrobial stewardship. Additional studies are needed especially in the Central African region. Future studies should be designed using standardized protocol and standardized definition to reduce heterogeneity among the studies.


Background
Healthcare-associated infections (HAIs) are a threat to patient safety during hospitalization. HAIs are associated with significant morbidity, mortality and healthcare costs, and they also impact negatively on patients' health-related quality of life [1,2]. In the United State, approximately 2 million HAIs are reported annually with about 90,000 deaths [3]. In Asia, HAIs prolonged hospital stay by 5-21 days and HAIs are associated with mortality ranging from 7% to 46% [2]. In Africa, a higher rate of mortality among inpatients who suffer HAIs has been reported (22.0%) [4]. In addition, HAIs are associated with multidrug resistant pathogens which constitutes a burden to patient's clinical and economic outcomes [5]. Existing data suggest that the burden of HAIs is higher in low and middle income countries compared to developed countries [6,7]. In the United States, HAIs affect about 4% of patients admitted to acute care health facilities [8], while 6.5% and 3.9% of patients in acute care hospitals and long-term care facilities in Europe have at least one HAI, respectively [9]. In Asia, it is estimated that 9.0% of hospitalized patients develop at least one HAI with higher incidence reported in the intensive care unit (ICU) [2]. There are limited data describing the burden of HAIs in healthcare facilities across Africa; however, it is estimated that the prevalence of HAIs is much higher than in developed countries [7,10]. Lack of infection prevention and control program and lack of hand hygiene training and infrastructure are some of the reasons responsible for the high rate of HAIs in Africa [11,12]. Most HAIs are preventable using evidence-based multifaceted infection control and prevention measures [1,13]. However, understanding the epidemiology of HAIs is a prerequisite for designing effective infection prevention and control interventions.
Point-prevalence surveys have been used in the US and by the European Centre for Disease Prevention and Control for surveillance of HAIs [8,9]. There is a lack of surveillance system to monitor HAIs in healthcare facilities across Africa. Previous estimate of HAIs in Africa was reported in a systematic reviewed conducted over 10 years ago [7]. In recent years, several point-prevalence studies conducted in healthcare facilities across Africa have been published. The primary objective of this study is to estimate the pooled point-prevalence and types of HAIs among hospitalized patients in Africa. The secondary objectives are to evaluate the risk factors associated with HAIs and to describe the microorganisms isolated from patients with HAIs in African studies.

Study design
This systematic review and meta-analysis of healthcareassociated infections in Africa was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement 2020 [14].

Information sources
Two electronic databases PubMed and Scopus were used to identify eligible articles. The databases were searched from 01/01/2010 to 04/03/2022 using the search terms described below. In addition, Google Scholar was also searched to find additional studies. The reference lists of selected studies was also examined for eligible articles.

Search strategy
The keywords "point-prevalence study", "healthcare associated infections", and "Africa" with their synonyms were combined using Boolean indicators.

Selection process
All the articles identified from the electronic databases were combined and screened to identify and remove duplicates. The titles and abstracts of the non-duplicate articles were screened by two independent reviewers (UA and OA) based on the eligibility criteria. The full-text of the studies that fulfil the eligibility criteria were reviewed for data collection by two reviewers (UA and OA). Disagreement between the reviewers was resolved through consensus.

Data collection process
The selected studies were reviewed and the data were collected using a predesigned data collection form. Data collection was conducted by two independent reviewers (UA and OA). Consensus was used to address any disagreements between the reviewers.

Data items
The following information was extracted from the selected studies: first author's name and year of publication, country involved, study setting/number of centre(s), study design, study period, number of patients involved, PPS protocol used (ECDC, CDC or as defined by the authors), overall prevalence of HAIs, types of HAIs and their prevalence, the risk factors associated with HAIs and their odds ratio, and the microorganisms that caused HAIs among the patients.

Quality assessment
The methodological quality of the selected studies was assessed by two independent reviewers (UA and OA) using the Newcastle-Ottawa scale (NOS) [15]. The NOS consists of three sections including selection, comparability, and outcomes. Disagreements between the reviewers were resolved through consensus.

Outcome assessment and effect measures
The primary outcome was the overall point-prevalence of HAIs among hospitalized patients in Africa. HAI was defined as an infection diagnosed among hospitalized patients which was not present or incubating at the time of admission. This definition is based on the Centers for Disease Control and Prevention (CDC) [16] and the European Centres for Disease Prevention and Control (ECDC) guidelines [17]. Secondary outcomes include types of HAIs and their prevalence among hospitalized patients as defined by the guidelines [16,17]. Other secondary outcomes include the risk factors associated with HAIs and the microorganisms that caused HAIs among hospitalized patients. The primary outcome was presented as frequency and percentage. The types of HAIs were presented as frequency and percentage. The risk factors associated with HAI were presented as adjusted odds ratio, while the microorganisms were retrieved as frequency and percentage.

Synthesis methods
The data were synthesized using both qualitative and quantitative methods. Quantitative synthesis was conducted using RevMan 5.4 software. The overall pointprevalence of HAIs was evaluated as the number of patients with HAI on the day of the survey as a proportion of all hospitalized patients on the day of the survey. The pooled estimate was determined using randomeffects meta-analysis. The selected studies were from different countries and the patient population varied. Therefore, our objective was to estimate the mean of a distribution of effects. The results were described using forest plots. Heterogeneity was examined using the Higgins I 2 statistic, with < 40% considered as low heterogeneity, 30-60% moderate heterogeneity, 50-90% substantial heterogeneity and 75-100% considerable heterogeneity [18]. To provide pooled risk estimates for the factors associated with HAIs, a meta-regression analysis was performed for risk factors found to be significant in at least two of the selected studies.

Study selection
A total of 6094 articles were identified from the electronic databases and 54 duplicates were removed. After screening the title and abstracts of the non-duplicate articles, 5967 articles were excluded. The full-text of 73 articles was reviewed and 13 eligible studies were selected. Two additional studies were found after checking the reference list of selected studies. Overall, 15 studies were included in this systematic review, while 11 studies were selected for the meta-analysis. Figure 1 shows the article screening and selection process.

Characteristics of selected studies
Six (40%) studies were conducted in North Africa (four from Tunisia and two from Morocco). West Africa (one each from Nigeria, Ghana and Benin Republic) and South Africa (two and one from South Africa and Botswana, respectively) had three studies each. In East Africa, one study was conducted in Ethiopia, Uganda and Malawi. Most studies (n = 9, 60.0%) involved multiple centres and 12 studies (80.0%) were hospital-wide point-prevalence studies (including multiple units in the hospital). One study each involved patients in a single unit/ward including ICU, surgery and paediatric/neonatal unit. Overall, a total of 11,272 hospitalized patients were included in the selected studies and the patient population ranged between 103 and 2107 patients. Table 1 summarizes the characteristics of the selected studies.

Quality Assessment
Overall, most of the studies (n = 12; 80%) have good quality. Two of the studies were found to have moderate quality, while one study had low quality. The sample were representative in 13 (86.7%) studies. There was low risk of bias in the assessment of outcomes and statistical test domains with 12 (80%) studies having good quality rating. Nine studies had a total score of 8 points, three studies had 7 points, while three studies had less than 6 points. Table 2 shows the quality assessment of the selected studies.

Pathogens involved in HAIs
Overall, only 37.9% of HAIs had documented positive microbiological culture result and the pathogens identified include bacteria and fungi. Gram negative bacteria including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter were the most common microorganisms and accounted for 40-100% of the pathogens. This was followed by gram positive bacteria such as Staphylococcus aureus, enterococci and streptococci, and fungi such as Candida albicans and Aspergillus fumigatus which account for 21.7-50% and 1.8-21.7%, respectively. Table 4 shows the distribution of the pathogens identified as causes of HAIs in African studies.

Discussion
This study evaluated the prevalence and types of HAIs, and pathogens implicated in those infections among hospitalized patients in Africa. The study found that there are limited studies that reported the rate of HAIs among hospitalized patients, particularly in the Central African region, where there was limited number of studies. The studies used different guidelines to conduct the pointprevalence studies reflecting the lack of an African protocol for conducting point-prevalence of HAIs in African hospitals. Therefore, the development and validation of a protocol for conducting point-prevalence studies in African hospitals is recommended and this can be spearheaded by the African Centres for Control and Prevention. Most of the studies included in this review had good quality and minimal risk of bias. The pooled prevalence of HAIs in Africa was about 12.8% and this is higher than the prevalence reported in Asia (9.0%) [2], Europe (6.5%) [9] and the United States (4.0%) [8]. However, the rate of HAIs is lower than the 15.5% reported in developing countries [6] and 16.9% reported in Ethiopia [33,34]. Higher rate of HAIs in Africa could be explained by poor infection control and prevention practices in the continent due to limited infection prevention and control capacity [35]. Previous studies have shown poor rate of adherence to hand hygiene among healthcare workers in sub-Saharan Africa due to lack of knowledge and training, heavy workload and lack of infrastructure [11]. Therefore, strategies to improve compliance with hand hygiene among healthcare workers including training, provision of soap and water as well as alcohol-based hand rub are recommended [12]. The improvement in hand and environmental hygiene during the COVID-19 pandemic may have an impact on the rate of HAIs in Africa but there is lack of evidence to demonstrate changes in the rate of HAIs during the pandemic. The prevalence of HAIs seems to be higher in the East African region and lower in the South African region. The reasons for this variations are unclear but it could be attributed to the use of different methods and tools to define HAIs among the studies. Further studies are required to confirm these observations. Existing evidence has shown that patients admitted into the ICU have higher risk of developing HAIs [8]. The current review confirms these data, with the finding of higher rate of HAIs in the ICU. This is in consonance with the finding of a meta-analysis in Ethiopia [33]. The result also revealed high rate of HAIs in neonatal and paediatric wards which is consistent with the findings of a previous systematic review and meta-analysis of HAIs in Ethiopia [10], and in developing countries [6]. Therefore, continuous HAIs   data revealed low compliance with the timing and duration of antimicrobial prophylaxis [37][38][39]. Therefore, antimicrobial stewardship and infection prevention and control are recommended to reduce the burden of surgical site infections in Africa [40]. Bloodstream infection and respiratory tract infections including pneumonia were the second and third most common HAIs in Africa. These infections are mostly device-associated and are preventable with appropriate infection prevention and control measures. Hand and environmental hygiene as well as injection safety practices should be encouraged in African healthcare facilities. The COVID-19 pandemic has caused significant disruption in healthcare systems including infection prevention and control [41][42][43][44]. The diversion of traditional infection prevention and control resources and measures, such as active surveillance; screening programme to detect colonization, and isolation of patients with multidrug resistant infections; to the management of the pandemic may increase the prevalence of HAIs [42][43][44][45]. In contrast, evidence has shown that healthcare workers had good infection control practices during the pandemic and this will reduce the transmission of HAIs [46]. However, there is a lack of data to describe the impact of COVID-19 pandemic on the prevalence of HAIs in healthcare facilities across Africa. Several risk factors have been reportedly associated with HAIs in African studies and our analysis revealed that those with history of recent hospitalization had the highest risk of HAIs, followed by the presence of peripheral vascular catheter and those with diabetes mellitus. Frequent hospitalization is more common in patients with multiple comorbidities or those with complicated chronic illnesses which predispose such patients to an increased risk of HAIs and colonization or infection with multidrug resistant pathogens. The use of peripheral vascular catheter increases the risk of bloodstream infection among hospitalized patients and this explains the association between HAIs and the presence of peripheral catheter in our study. Patients with diabetes mellitus have an increased risk of common infections compared to those without diabetes mellitus [47]. The current review confirmed these data with the finding of higher risk of HAIs among diabetes mellitus patients in Africa. This finding is consistent with a previous meta-analysis in Ethiopia that showed a significant association between HAIs and underlying non-communicable disease [33]. Therefore, efforts to achieve and maintain glycaemic control among diabetes mellitus patients during hospitalization is recommended in addition to improved hand and environmental hygiene practices. Other factors significantly associated with HAIs in Africa include admission into surgical ward and underlying ultimately fatal McCabe score.
The current review revealed that gram negative pathogens such as E. coli, K. pneumoniae, P. aeruginosa and A. baumannii were the most common causative organisms associated with HAIs. This is consistent with findings of a previous systematic reviews [2,6]. Other pathogens include gram positive bacteria and fungi, such as C. albicans and A. fumigatus. The current review has a number of limitations that warrant caution in interpreting the results. Firstly, there was limited number of pointprevalence studies conducted in Central African region and limited number of studies from the other regions. This may potentially affect the generalizability of the results. Secondly, the degree of heterogeneity was high and this was lower than the heterogeneity reported in a previous systematic review and meta-analysis [6]. Differences in study protocol, data collection method, study period, and definition of HAIs between the studies may explain the high degree of heterogeneity. Future studies should develop and validate an African protocol for point-prevalence survey of HAIs in African hospitals. This will bring about consistency in the design, data collection and description of HAIs in Africa. The African CDC should develop a standardise protocol for conducting point-prevalence studies for HAIs in Africa to ensure consistency between studies. Thirdly, the reporting of point-prevalence studies of HAIs in Africa need to improve as many studies did not describe the confidence interval for the point-prevalence of HAIs in different wards/units and the confidence interval for the different types of HAIs. This made it difficult to perform a detailed meta-analysis. Studies describing the impact of HAIs on morbidity, mortality, quality of life and the economic burden of HAIs in Africa are recommended.

Conclusions
The pooled point-prevalence of HAIs in Africa is relatively high compared to the other continents. The pointprevalence of HAIs in Africa is about two times higher than the rate reported in developed countries. The point-prevalence of HAIs is higher in ICU and neonatal wards compared to the other wards. Surgical site infections and bloodstream infection were the most common HAIs reported in Africa. Recent hospitalization, presence of peripheral vascular catheter and having diabetes mellitus were the strongest risk factors associated with HAIs in Africa. Gram negative bacteria were the major causative pathogens associated with HAIs. Infection prevention and control measures and antimicrobial stewardship are recommended to reduce the burden of HAIs among hospitalized patients in Africa.